基于网络药理学的茯苓-甘草药物对治疗紫癜性肾炎的分子靶点和机制研究

Jiahua Liu, Qingqing Liu, Xiaoqin Ma, Weiyan Guo, Jie Mi
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摘要

背景:中药茯苓甘草合剂(PLDP)具有利尿、健脾、益肾的作用,在治疗白癜风肾炎(HSPN)中发挥着重要作用。然而,其作用机制尚不清楚。研究目的通过网络药理学的方法,本研究试图确定 PLDP 对 HSPN 的作用机制。材料与方法:通过中药系统药理学(TCMSP)数据库筛选 PLDP 中的有效成分,并从 TCMSP 和瑞士靶点预测(STP)数据库中获取其靶点。HSPN的基因则通过OMIM、DisGeNET和GeneCards数据库进行检索。然后,通过文氏分析法绘制了 PLDP 和 HSPN 中活性成分的共同靶标。为了获得主要靶点,研究人员利用 STRING 数据库构建了共同靶点的蛋白质-蛋白质相互作用(PPI)网络。然后,研究人员在Metascape数据库中研究了主要靶点的基因本体(GO)功能和京都基因组百科全书(KEGG)通路的富集情况,以确定PLDP对抗HSPN的分子机制。从排名前 20 的通路中筛选出与 HSPN 最相关的信号通路,并将其定义为关键通路。最后,建立 "活性成分-主要靶点-关键通路 "网络,以确定 PLDP 对抗 HSPN 的核心靶点和关键活性成分。结果PLDP共有101种活性成分和360个靶点。确定了 157 个 HSPN 基因和 35 个 PLDP 与 HSPN 的共同靶点。通过 "有效成分-主要靶点-关键通路 "网络,槲皮素、山柰酚、多酚酸C、脱氢木糖酸、多孔菌酸A和柚皮苷被确定为关键有效成分;TNF、NOS3、RELA、AKT1、ICAM1和IFNG被确定为核心靶点;关键通路包括TNF信号通路、HIF-1信号通路和IL-17信号通路。结论该研究初步探明了 PLDP 抗 HSPN 所涉及的途径、活性成分和靶点。其机制似乎与其免疫调节和抗炎特性有关,从而为进一步研究奠定了科学基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular Targets and Mechanisms of Poria cocos-Licorice Drug Pair for the Treatment of Henoch–Schönlein Purpura Nephritis Based on Network Pharmacology
Background: The herbal Poria cocos-Liquorice drug pair (PLDP) possesses the ability to be a diuretic, stimulating the spleen and benefiting the kidney, which plays an important role in the treatment of Henoch–Schönlein purpura nephritis (HSPN). However, the mechanism of action is unknown. Objectives: Through the method of network pharmacology, this research sought to determine the mechanism of PLDP against HSPN. Materials and Methods: The screening of active ingredients in PLDP was conducted by Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases, while their targets were obtained from the TCMSP and Swiss Target Prediction (STP) databases. The genes of HSPN were searched by OMIM, DisGeNET, and GeneCards databases. Then, the common targets of active ingredients in PLDP and HSPN were mapped by Venn analysis. To get the main targets, the researchers utilized the STRING database to construct the protein–protein interaction (PPI) network of the common targets. Then, the function of gene ontology (GO) and the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the main targets were examined on the Metascape database to identify the molecular mechanism of PLDP against HSPN. The most relevant signaling pathways with HSPN screened from the top 20 pathways were defined as the key pathways. Finally, the “active ingredient-main target-key pathway” network was built in order to identify the core targets and key active ingredients of PLDP against HSPN. Results: There were 101 active ingredients and 360 targets for PLDP. One hundred and fifty-seven genes for HSPN and 35 common targets between PLDP and HSPN were identified. Through the “active ingredient-main target-key pathway” network, quercetin, kaempferol, polyporenic acid C, dehydrotumulosic acid, poricoic acid A, and naringenin were identified as key active ingredients; TNF, NOS3, RELA, AKT1, ICAM1, and IFNG were identified as core targets; and the key pathways include TNF signaling pathways, HIF-1 signaling pathways, and IL-17 signaling pathways. Conclusion: The research initially investigated the pathways, active ingredients, and targets involved in PLDP against HSPN. The mechanism appears to be linked to its immunomodulatory and anti-inflammatory properties, thus establishing a scientific foundation for further investigation.
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